Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma
Menée sur 297 patients atteints d'un carcinome hépatocellulaire et sur 631 témoins, cette étude prospective chinoise évalue l'association entre les niveaux sériques avant diagnostic de métabolites du métabolisme monocarboné (bétaïne, choline, cystathionine, ...) et le risque de développer la maladie
Background : Rats fed diets deficient in choline develop hepatocellular carcinoma (HCC). Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and HCC risk have been lacking. Methods : We prospectively examined the association between prediagnostic serum concentrations of one-carbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing HCC based on a nested case-control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate odds ratios (OR) and 95% confidence intervals (CI) adjusted for established risk factors for HCC. Results: Serum choline and PLP were associated with statistically significant reduced risk of HCC, while serum cystathionine, methionine and SAM were associated with increased HCC risk (all Ptrend<0.05). The inverse associations for HCC risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16, 0.78) (P=0.010) and 0.44 (0.25, 0.78) (P=0.005), respectively. There were no associations for HCC risk with 5-MTHF, betaine, or homocysteine. Conclusion : The inverse associations between choline and vitamin B6 and the risk of HCC development are novel and warrant further investigation. Impact: Identifying new modifiable factors for HCC prevention are warranted.